Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk
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Typ dokumentu preprinty, časopisecké články
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R01 CA074850
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PubMed
38496424
PubMed Central
PMC10942532
DOI
10.1101/2024.02.29.24303243
PII: 2024.02.29.24303243
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
- preprinty MeSH
BACKGROUND: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). METHODS: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. RESULTS: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). CONCLUSIONS: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.
Aix Marseille Université INSERM IRD SESSTIM Marseille France
AnaNeo Therapeutics New York NY USA
Assuta Medical Center Tel Aviv Israel
Basser Center for BRCA Abramson Cancer Center University of Pennsylvania Philadelphia PA USA
BMC Faculty of Medicine University of Iceland Reykjavik Iceland
Cancer Epidemiology Division Cancer Council Victoria East Melbourne Victoria Australia
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Cancer Genetics and Prevention Program University of California San Francisco San Francisco CA USA
Cancer Genetics Group IPO Porto Research Center Porto Comprehensive Cancer Center Porto Portugal
Cancer Genetics Laboratory Peter MacCallum Cancer Centre Melbourne Victoria Australia
Cancer Prevention and Control Program Rutgers Cancer Institute of New Jersey New Brunswick NJ USA
Cancer Registry of Norway Norwegian Institute of Public Health Oslo Norway
Cancer Research Institute Ghent Ghent Belgium
Cancer Research UK Cambridge Institute University of Cambridge Cambridge UK
Carmel Medical Center Haifa Israel
Center for Bioinformatics and Functional Genomics Cedars Sinai Medical Center Los Angeles CA USA
Center for Clinical Cancer Genetics The University of Chicago Chicago IL USA
Center for Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Center for Medical Genetics NorthShore University HealthSystem Evanston IL USA
Centre for Cancer Biomarkers CCBIO Department of Clinical Science University of Bergen Bergen Norway
Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge UK
Centre for Medical Genetics Ghent University Gent Belgium
Centro de Investigación en Red de Enfermedades Raras Madrid Spain
Chronic Disease Epidemiology Yale School of Medicine New Haven CT USA
City of Hope Clinical Cancer Genetics Community Research Network Duarte CA USA
Clinical Cancer Epidemiology Institute of Cancer Research London UK
Clinical Cancer Genomics City of Hope Duarte CA USA
Clinical Cancer Research Center Aalborg University Hospital Aalborg Denmark
Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK
Clinical Genome Center Department of Clinical Research University of Southern Denmark Odense Denmark
Département de Biopathologie Centre François Baclesse Caen France
Department of Biomedical Data Science Stanford University School of Medicine Stanford CA USA
Department of Biomolecular Medicine University of Ghent Ghent Belgium
Department of Breast Medical Oncology University of Texas MD Anderson Cancer Center Houston TX USA
Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Cancer Epidemiology Moffitt Cancer Center Tampa FL USA
Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA
Department of Clinical Genetics Helsinki University Hospital University of Helsinki Helsinki Finland
Department of Clinical Genetics Maastricht University Medical Center Maastricht The Netherlands
Department of Clinical Genetics Odense University Hospital Odense Denmark
Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Clinical Medicine Aalborg University Aalborg Denmark
Department of Computational Biomedicine Cedars Sinai Medical Center Los Angeles CA USA
Department of Epidemiology Colorado School of Public Health University of Colorado Aurora CO USA
Department of Epidemiology Harvard T H Chan School of Public Health Boston MA USA
Department of Epidemiology University of Michigan School of Public Health Ann Arbor MI USA
Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX USA
Department of Epidemiology University of Washington Seattle WA USA
Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA
Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland
Department of Gynaecological Oncology Westmead Hospital Sydney New South Wales Australia
Department of Gynecologic Oncology Duke University Hospital Durham NC USA
Department of Gynecology and Gynecologic Oncology Kliniken Essen Mitte Essen Germany
Department of Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY USA
Department of Human and Medical Genetics Faculty of Medicine Vilnius University Vilnius Lithuania
Department of Internal Medicine Division of Human Genetics The Ohio State University Columbus OH USA
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA
Department of Medical Oncology University Hospital of Vall d'Hebron Barcelona Spain
Department of Medicine Huntsman Cancer Institute University of Utah Health Salt Lake City UT USA
Department of Medicine Stanford University School of Medicine Stanford University Stanford CA USA
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Department of Molecular Genetics University of Toronto Toronto ON Canada
Department of Molecular Medicine Faculty of Medicine Université Laval Québec City QC Canada
Department of Molecular Oncology BC Cancer Research Centre Vancouver BC Canada
Department of Obstetrics and Gynecology Brigham and Women's Hospital Boston MA USA
Department of Obstetrics and Gynecology Haukeland University Hospital Bergen Norway
Department of Obstetrics and Gynecology Providence Medical Center Medford OR USA
Department of Obstetrics and Gynecology University of British Columbia Vancouver BC Canada
Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville TN USA
Department of Obstetrics Gynecology and Reproductive Biology Harvard Medical School Boston MA USA
Department of Oncology Biobank National Institute of Oncology Budapest Hungary
Department of Oncology Mayo Clinic Rochester MN USA
Department of Pathology and Laboratory Medicine University of British Columbia Vancouver BC Canada
Department of Pathology Landspitali the National University Hospital of Iceland Reykjavik Iceland
Department of Population Sciences Beckman Research Institute of City of Hope Duarte CA USA
Department of Public Health Sciences University of Virginia Charlottesville VA USA
Department of Quantitative Health Sciences Mayo Clinic College of Medicine Rochester MN USA
Department of Radiation Oncology Hannover Medical School Hannover Germany
Department of Tumor Growth Biology N N Petrov Institute of Oncology St Petersburg Russia
Dept of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Cancer Prevention and Genetics IEO European Institute of Oncology IRCCS Milan Italy
Division of Gynecologic Oncology University Hospital Leuven Leuven Belgium
Epidemiology Branch National Institute of Environmental Health Sciences NIH Rockville MD USA
Escola de Doutoramento Internacional Universidade de Santiago Santiago de Compostela Spain
Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia
Familial Cancer Clinical Unit Human Cancer Genetics Programme Madrid Spain
Fundación Pública Galega de Medicina Xenómica Santiago de Compostela Spain
Genetics Department Institut Curie Paris France
Genome Diagnostics Program IFOM the FIRC Institute of Molecular Oncology Milan Italy
Gynaecology Research Unit Hannover Medical School Hannover Germany
Health Informatics Institute Morsani College of Medicine University of South Florida Tampa FL USA
Hereditary Cancer Genetics Group Vall d'Hebron Institute of Oncology Barcelona Spain
Hereditary Cancer Program IDIBELL Catalan Institute of Oncology Barcelona Spain
Hereditary Cancer Program Kaiser Permanente Northern California San Francisco CA USA
Human Genotyping Unit CeGen Spanish National Cancer Research Centre Madrid Spain
Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Institute of Cancer Sciences University of Glasgow Glasgow UK
Institute of Human Genetics University Hospital Heidelberg Heidelberg Germany
Leuven Cancer Institute University of Leuven Leuven Belgium
Lombardi Comprehensive Cancer Center Georgetown University Washington DC USA
Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Canada
Magee Womens Hospital University of Pittsburgh School of Medicine Pittsburgh PA USA
Medical Birth Registry of Norway Norwegian Institute of Public Health Norway
Medical Genetics Unit St George's University of London London UK
Mines ParisTech Fontainebleau France
Molecular Diagnostics Aalborg University Hospital Aalborg Denmark
Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany
Molecular Oncology Laboratory CIBERONC Hospital Clinico San Carlos IdISSC Madrid Spain
MRC Integrative Epidemiology Unit University of Bristol Bristol UK
N N Alexandrov Research Institute of Oncology and Medical Radiology Minsk Belarus
National Tumour Biology Laboratory National Institute of Oncology Budapest Hungary
Population Health Program QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
Princess Margaret Cancer Center Toronto Canada
ProCURE IDIBELL Catalan Institute of Oncology Barcelona Spain
ProCURE IDIBGI Catalan Institute of Oncology Girona Spain
Providence Cancer Center Medford OR USA
PSL Research University Paris France
Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands
Roswell Park Comprehensive Cancer Center Buffalo NY USA
Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel
Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne Victoria Australia
SOD Genetica Molecolare University Hospital Pisa Italy
Spanish Network on Rare Diseases Madrid Spain
Stanford Cancer Institute Stanford University School of Medicine Stanford University Stanford CA USA
State Research Institute Centre for Innovative Medicine Vilnius Lithuania
Technion Israel Institute of Technology Haifa Israel
The Association for Promotion of Research in Precision Medicine Haifa Israel
The Susanne Levy Gertner Oncogenetics Unit Chaim Sheba Medical Center Ramat Gan Israel
The University of Chicago Pritzker School of Medicine Chicago IL USA
Ufa University of Science and Technology Ufa Russia
Unité INSERM U830 Paris France
Université Paris Cité Paris France
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